HRP20210965T1 - Derivati pirazolilaminobenzimidazola kao jak inhibitori - Google Patents

Derivati pirazolilaminobenzimidazola kao jak inhibitori Download PDF

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Publication number
HRP20210965T1
HRP20210965T1 HRP20210965TT HRP20210965T HRP20210965T1 HR P20210965 T1 HRP20210965 T1 HR P20210965T1 HR P20210965T T HRP20210965T T HR P20210965TT HR P20210965 T HRP20210965 T HR P20210965T HR P20210965 T1 HRP20210965 T1 HR P20210965T1
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HR
Croatia
Prior art keywords
compound according
pharmaceutically acceptable
image
acceptable salt
amino
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Application number
HRP20210965TT
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English (en)
Inventor
Jolie Anne Bastian
Joshua Ryan Clayton
David Andrew Coates
Daniel Jon Sall
Timothy Andrew WOODS
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Eli Lilly And Company
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Publication of HRP20210965T1 publication Critical patent/HRP20210965T1/hr

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/41841,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Claims (19)

1. Spoj formule, ili njegova farmaceutski prihvatljiva sol [image] gdje R je izabran između: H, -C1-3 alkil, -CH2CH(OH)CH3, -C2-3 alkil-O-CH3, [image] R1 je izabran između: H, -CH3, i -OCH3; R2 je -CHF2 ili -CF3; i R3 je H ili -CH3; uz uvjet da kada R2 je -CF3 i R3 je H, ili R ili R1 mogu biti -CH3, ali ne oba.
2. Spoj prema zahtjevu 1 formule, ili njegova farmaceutski prihvatljiva sol, [image] gdje: R je izabran između: H, -C1-3 alkil, -CH2CH(OH)CH3, -C2-3 alkil-O-CH3, [image] i [image] R1 je izabran između: H, -CH3, i -OCH3; R2 je -CHF2 ili -CF3; i R3 je H ili -CH3; uz uvjet da kad R2 je -CF3, i R3 je H, ili R ili R1 mogu biti -CH3, ali ne oba.
3. Spoj prema zahtjevu 1 ili 2 gdje R je izabran između: -CH3, -CH2CH3, i [image] ili njegova farmaceutski prihvatljiva sol.
4. Spoj prema bilo kojem od zahtjeva 1 do 3 gdje R je -CH3, ili -CH2CH3, ili njegova farmaceutski prihvatljiva sol.
5. Spoj prema bilo kojem od zahtjeva 1 do 3 gdje R je [image] ili njegova farmaceutski prihvatljiva sol.
6. Spoj prema bilo kojem od zahtjeva 1 do 5 gdje R2 je -CF3, ili njegova farmaceutski prihvatljiva sol.
7. Spoj prema bilo kojem od zahtjeva 1 do 6 gdje R3 je -CH3, ili njegova farmaceutski prihvatljiva sol.
8. Spoj prema bilo kojem od zahtjeva 1 do 4 koje je [image] ili njegova farmaceutski prihvatljiva sol.
9. Spoj prema bilo kojem od zahtjeva 1 do 4 koje je [image] ili njegova farmaceutski prihvatljiva sol.
10. Spoj prema zahtjevu 1 ili 2 koje je [image] ili njegova farmaceutski prihvatljiva sol.
11. Spoj prema bilo kojem od zahtjeva 1 do 3, ili 5 koje je [image] ili njegova farmaceutski prihvatljiva sol.
12. Spoj prema bilo kojem od zahtjeva 1 do 3, ili 5 koje je (2R)-1,1,1-trifluoro-3-({cis-4-[(1-metil-4-{[1-(piridin-2-il)-1H-pirazol-3-il]amino}-1H-benzimidazol-6-il)oksi]cikloheksil}amino)propan-2-ol2-hidroksipropan-1,2,3-trikarboksilat hidrat.
13. Spoj prema bilo kojem od zahtjeva 1 do 3, ili 5 koje je (2R)-1,1,1-trifluoro-3-({cis-4-[(1-metil-4-{[1-(piridin-2-il)-1H-pirazol-3-il]amino}-1H-benzimidazol-6-il)oksi]cikloheksil}amino)propan-2-ol u kristalnom obliku karakteriziranom spektrom difrakcije X-zraka na prahu dobivenom sa CuKa izvorom (λ=1.54060 Å), koji ima signal na 20.5 u kombinaciji sa jednim ili više signala izabranih iz grupe koju čine 15.5, 18.1, 18.3, 18.5, 22.9 i 23.6; sa odstupanjem difrakcijskih uglova od 0.2 stupnjeva.
14. Spoj prema bilo kojem od zahtjeva 1 do 3, ili 5 koje je (2R)-1,1,1-trifluoro-3-({cis-4-[(1-metil-4-{[1-(piridin-2-il)-1H-pirazol-3-il]amino}-1H-benzimidazol-6-il)oksi]cikloheksil}amino)propan-2-ol 2-hidroksipropan-1,2,3-trikarboksilat hidrat u kristalnom obliku karakteriziranom spektrom difrakcije X-zraka na prahu dobivenom pomoću CuKa izvora (λ=1.54060 Å), koji ima signal na 17.9 u kombinaciji sa jednim ili više signala izabranih iz grupe koju čine 26.1, 26.6 i 22.7; sa odstupanjem difrakcijskih uglova od 0.2 stupnjeva.
15. Farmaceutski sastav koji sadrži spoj prema bilo kojem od zahtjeva 1 do 14 i farmaceutski prihvatljiv nositelj, razblaživač ili ekscipijent.
16. Farmaceutski sastav prema zahtjevu 15 koji sadrži više od 80% m/m spoja koji je (2R)-1,1,1-trifluoro-3-({cis-4-[(1-metil-4-{[1-(piridin-2-il)-1H-pirazol-3-il]amino}-1H-benzimidazol-6-il)oksi]cikloheksil}amino)propan-2-ol2-hidroksipropan-1,2,3-trikarboksilat hidrat u kristalnom obliku.
17. Farmaceutski sastav prema zahtjevu 15 koja sadrži više od 90 % m/m spoja koji je (2R)-1,1,1-trifluoro-3-({cis-4-[(1-metil-4-{[1-(piridin-2-il)-1H-pirazol-3-il]amino}-1H-benzimidazol-6-il)oksi]cikloheksil}amino)propan-2-ol2-hidroksipropan-1,2,3-trikarboksilat hidrat u kristalnom obliku.
18. Spoj prema bilo kojem od zahtjeva 1 do 14 za upotrebu u liječenju.
19. Spoj prema bilo kojem od zahtjeva 1 do 14 za upotrebu u liječenju artritisa.
HRP20210965TT 2016-07-14 2021-06-17 Derivati pirazolilaminobenzimidazola kao jak inhibitori HRP20210965T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662362208P 2016-07-14 2016-07-14
EP17740885.3A EP3484875B1 (en) 2016-07-14 2017-07-10 Pyrazolylaminobenzimidazole derivatives as jak inhibitors
PCT/US2017/041388 WO2018013486A1 (en) 2016-07-14 2017-07-10 Pyrazolylaminobenzimidazole derivatives as jak inhibitors

Publications (1)

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HRP20210965T1 true HRP20210965T1 (hr) 2021-09-17

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US (2) US10323019B2 (hr)
EP (1) EP3484875B1 (hr)
JP (1) JP6712331B2 (hr)
KR (1) KR102225840B1 (hr)
CN (1) CN109476643B (hr)
AU (1) AU2017296026B2 (hr)
BR (1) BR112018075086B1 (hr)
CA (1) CA3030697C (hr)
CY (1) CY1124308T1 (hr)
DK (1) DK3484875T3 (hr)
EA (1) EA038129B1 (hr)
ES (1) ES2877198T3 (hr)
HR (1) HRP20210965T1 (hr)
HU (1) HUE054912T2 (hr)
LT (1) LT3484875T (hr)
MX (1) MX2019000542A (hr)
NZ (1) NZ748942A (hr)
PL (1) PL3484875T3 (hr)
PT (1) PT3484875T (hr)
RS (1) RS61991B1 (hr)
SI (1) SI3484875T1 (hr)
WO (1) WO2018013486A1 (hr)

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KR20230141115A (ko) 2022-03-31 2023-10-10 한림대학교 산학협력단 신규한 2-아릴-1H-벤조[d]이미다졸 유도체, 이의 제조 방법 및 이의 항암제로서의 용도
KR102582097B1 (ko) 2022-12-28 2023-09-25 (주)메디언스 야누스키나아제 표적 억제제 및 이의 용도

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JP2010524911A (ja) * 2007-04-18 2010-07-22 アストラゼネカ アクチボラグ 5−アミノピラゾール−3−イル−3H−イミダゾ[4,5−b]ピリジン誘導体と癌の治療のためのその使用
US8445676B2 (en) * 2008-10-08 2013-05-21 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
WO2010068806A1 (en) * 2008-12-10 2010-06-17 Cgi Pharmaceuticals, Inc. Amide derivatives as btk inhibitors in the treatment of allergic, autoimmune and inflammatory disorders as well as cancer
CN102712640A (zh) * 2010-01-12 2012-10-03 弗·哈夫曼-拉罗切有限公司 三环杂环化合物、其组合物和应用方法
AR083933A1 (es) * 2010-11-19 2013-04-10 Incyte Corp Derivados de pirrolopiridina y pirrolopirimidina sustituidos con ciclobutilo como inhibidores de jak
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SI3484875T1 (sl) 2021-08-31
MX2019000542A (es) 2019-07-04
EP3484875B1 (en) 2021-04-07
CN109476643B (zh) 2021-06-08
JP6712331B2 (ja) 2020-06-17
WO2018013486A1 (en) 2018-01-18
HUE054912T2 (hu) 2021-10-28
EP3484875A1 (en) 2019-05-22
PT3484875T (pt) 2021-07-05
CA3030697A1 (en) 2018-01-18
KR102225840B1 (ko) 2021-03-11
US10344018B2 (en) 2019-07-09
BR112018075086A2 (pt) 2019-03-12
DK3484875T3 (da) 2021-06-28
ES2877198T3 (es) 2021-11-16
RS61991B1 (sr) 2021-07-30
JP2019525908A (ja) 2019-09-12
EA201892698A1 (ru) 2019-06-28
NZ748942A (en) 2020-08-28
KR20190015561A (ko) 2019-02-13
AU2017296026A1 (en) 2018-12-20
CN109476643A (zh) 2019-03-15
AU2017296026B2 (en) 2019-11-21
CY1124308T1 (el) 2022-07-22
US20190177300A1 (en) 2019-06-13
US10323019B2 (en) 2019-06-18
CA3030697C (en) 2021-02-23
LT3484875T (lt) 2021-07-26
PL3484875T3 (pl) 2021-11-02
US20180325873A1 (en) 2018-11-15
BR112018075086B1 (pt) 2024-02-27
EA038129B1 (ru) 2021-07-09

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